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Oliver W Gramlich, Amy C Cook, Sabine Beck, Norbert Pfeiffer, Franz H Grus, Markus H Kuehn; Correlative analysis of clinical findings, autoimmune characteristics and complement activation in human glaucomatous eyes. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5696.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cell degeneration in glaucoma is linked to neuroinflammatory processes, including complement activation, and an autoimmune involvement. The autoimmune component is characterized by retinal autoantibody accumulation and changes in the serum autoantibody patterns. This study aims to determine correlations between autoantibodies, complement proteins and clinical observations in the same glaucoma patients.
IgG, C3, and C5b-9 depositions were examined immunohistologically in donor retinae of 15 healthy subjects (ctrl) and 15 primary open angle glaucoma patients (POAG) with advanced (n=7), moderate (n=4) and early (n=4) disease. Post mortem blood samples from these donors were used to determine the autoantibody patterns against 70 antigens using antigen microarrays. A global normalization coefficient was applied and statistical comparison of normalized intensity for each antibody reactivity was performed. Autoantibody reactivities, IgG histology and clinical data were analyzed for correlation.
IgG depositions in the retinal ganglion cell layer are observed both in control and POAG eyes, but the amount in glaucomatous samples is significantly increased (ctrl: 0.9±0.7 IgG/100 cells, POAG: 1.5±0.8 IgG/100 cells; p=0.036). C3 and C5b-9 are exclusively seen in glaucoma subjects and very few C5b-9 depositions co-localize with IgG accumulations. Microarray analysis revealed the typical complex antibody patterns with several up and down regulations. IgG levels against Glucosidase II are significantly increased in POAG (p=0.03) and titers are positively correlated with disease stage (R2=0.93). In contrast, anti-Munc18-1 titers are negatively correlated to disease stage (R2=0.96) and the highest titers were observed in early glaucoma donors. Overall, anti-Munc18-1 titers are significantly increased in POAG (p=0.04) when compared to controls.
Using immunohistochemical approaches, a correlation between retinal IgG accumulation, complement deposition and glaucoma stage could not be established. However, some antigen-autoantibody reactions seems to correlate with the progression stage. Whether retinal IgG autoantibodies, especially in combination with complement proteins, have profound pathogenic impact, needs further investigation.
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